{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T10:30:23Z","timestamp":1791109823356,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,11,18]],"date-time":"2004-11-18T00:00:00Z","timestamp":1100736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We introduce a new approach to crystal\u2010packing analysis, based on the study of mutual recognition modes of entire molecules or of molecular moieties, rather than a search for selected atom\u2013atom contacts, and on the study of crystal energy landscapes over many computer\u2010generated polymorphs, rather than a quest for the one most stable crystal structure. The computational tools for this task are a polymorph generator and the PIXEL density sums method for the calculation of intermolecular energies. From this perspective, the molecular recognition, crystal packing, and solid\u2010state phase behavior of caffeine and several methylxanthines (purine\u20102,6\u2010diones) have been analyzed. Many possible crystal structures for anhydrous caffeine have been generated by computer simulation, and the most stable among them is a thermodynamic, ordered equivalent of the disordered phase, revealed by powder X\u2010ray crystallography. Molecular recognition energies between two caffeine molecules or between caffeine and water have been calculated, and the results reveal the largely predominant mode to be the stacking of parallel caffeine molecules, an intermediately favorable caffeine\u2013water interaction, and many other equivalent energy minima for lateral interactions of much less stabilization power. This last indetermination helps to explain why caffeine does not crystallize easily into an ordered anhydrous structure. In contrast, the mono\u2010 and dimethylxanthines (theophylline, theobromine, and the 1,7\u2010isomer, for which we present a single\u2010crystal X\u2010ray study and a lattice energy landscape) do crystallize in anhydrous form thanks to the formation of lateral hydrogen bonds.<\/jats:p>","DOI":"10.1002\/chem.200400499","type":"journal-article","created":{"date-parts":[[2004,11,18]],"date-time":"2004-11-18T12:18:49Z","timestamp":1100780329000},"page":"271-279","source":"Crossref","is-referenced-by-count":62,"title":["Molecular Recognition and Crystal Energy Landscapes: An X\u2010ray and Computational Study of Caffeine and Other Methylxanthines"],"prefix":"10.1002","volume":"11","author":[{"given":"Lucia","family":"Carlucci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Gavezzotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,12,15]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1039\/a702041d"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010188923713"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar00046a004"},{"key":"e_1_2_7_4_2","unstructured":"Gaussian 98 (Revision A.11) M. 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